Chemist interested in cannabinoid purification, identification, synthesis & formulation

[b3lyp631g]

I'm a PhD chemist working mostly in the clean tech industry, but I've got a little side hustle going on where I help researchers and clients working in the hemp and cannabis industries with purification, isolation, synthesis, and custom formulation. (I also help interpret sketchy COAs). I've been involved with a pretty wide array of projects and have noticed a lot of misinformation in the hemp and cannabis communities, so I'm here to answer questions. Reach out if you have any burning questions. I am very much not an expert in plant biology or cannabis cultivation, so I'm also here to learn what it's like to grow and distribute cannabis products.

 

[johnursery]

Just wanted to drop some appreciation on your intro, thank you for helping the industry. It's exciting times with delta-8 and seeing different cannabinoids being isolated or synthesized. I'm definitely a flower guy but I love concentrates too

 

[RippedTorn]

Which microbes will most efficiently synthesize 2-arachidonoyl-glycerol?

Or are you one of them cancer/manmade chemists?

 

[b3lyp631g]

Which microbes will most efficiently synthesize 2-arachidonoyl-glycerol?

Or are you one of them cancer/manmade chemists?

I'm not a biochemist, if that's what you're asking. I'm a synthetic organic chemist, so I'm more one the path of you give me a gram of CBD isolate and I turn it into a 0.998 grams of d8THC.

One of my buddies actually is a biochemist, and he uses yeast to biosynthesize cannabinoids. It's super inefficient right now. They're like give them a liter of yeast culture and you get .008 g of THC. That said, in the long-term, biosynthesis is almost always better for complicated natural products. I don't think cannabinoids are complicated, though.

Here's a link because scientists love references.

Scientists brew cannabis using hacked beer yeast

Researchers modify microbe to manufacture cannabis compounds including the psychoactive chemical THC.

www.nature.com

 

[beluga]

I don't have any questions, I'm just interested in what might-could ensue in this thread.
Good ol' Rip over here will surely keep it spicy.

Welcome to the farm!


⚗!

 

[MIMedGrower]

I'm not a biochemist, if that's what you're asking. I'm a synthetic organic chemist, so I'm more one the path of you give me a gram of CBD isolate and I turn it into a 0.998 grams of d8THC.

One of my buddies actually is a biochemist, and he uses yeast to biosynthesize cannabinoids. It's super inefficient right now. They're like give them a liter of yeast culture and you get .008 g of THC. That said, in the long-term, biosynthesis is almost always better for complicated natural products. I don't think cannabinoids are complicated, though.

Here's a link because scientists love references.

Scientists brew cannabis using hacked beer yeast

Researchers modify microbe to manufacture cannabis compounds including the psychoactive chemical THC.

www.nature.com

Singular cannabanoids (cbd, thc) alone have very little effect. The magic and the medicine in our plant comes from an entourage effect of a mix of cannabanoids and terpenes and maybe more we have not discovered.


The isolation of thc and cbd have already caused a “dumbing down” of what we want in breeding. Short flowering plants with tons of thc. But the best medicine comes from long flowering plants with more diverse canabanoids content and more terpenes.

any thought about this?

 

[b3lyp631g]

Singular cannabanoids (cbd, thc) alone have very little effect. The magic and the medicine in our plant comes from an entourage effect of a mix of cannabanoids and terpenes and maybe more we have not discovered.


The isolation of thc and cbd have already caused a “dumbing down” of what we want in breeding. Short flowering plants with tons of thc. But the best medicine comes from long flowering plants with more diverse canabanoids content and more terpenes.

any thought about this?

I generally agree - I personally wouldn't go out and buy a CBD or THC extract for consumption. My favorite running project is a collaboration with a research group at UC Berkeley wherein they've bred a large variety of new hemp strains by pretty traditional methods and I've helped them isolate, quantify, and identify the >40 cannabinoids in their hemp. In chemistry, isolation is usually a necessary prerequisite to identification. Most analytical methods like mass spectroscopy don't work with a large mixture of unknown cannabinoids since they're largely all isomers of one another (they have the same atoms, just bound together differently). We know of about 120 phytocannabinoids (that number is somewhat contested), and it's pretty exciting to see the mixtures present in what this team has grown. They're using the full spectrum extracts to treat anxiety and pain in cancer patients, and they'd like to know what's in the mix.

 

[Milson]

Can you explain "the entourage effect" as you understand it?

 

[OjoDeMalo]

I'm not a biochemist, if that's what you're asking. I'm a synthetic organic chemist, so I'm more one the path of you give me a gram of CBD isolate and I turn it into a 0.998 grams of d8THC.

One of my buddies actually is a biochemist, and he uses yeast to biosynthesize cannabinoids. It's super inefficient right now. They're like give them a liter of yeast culture and you get .008 g of THC. That said, in the long-term, biosynthesis is almost always better for complicated natural products. I don't think cannabinoids are complicated, though.

Here's a link because scientists love references.

Scientists brew cannabis using hacked beer yeast

Researchers modify microbe to manufacture cannabis compounds including the psychoactive chemical THC.

www.nature.com

Love me some citations and sources!!! right on!

 

[b3lyp631g]

Can you explain "the entourage effect" as you understand it?

I'll take a crack at it and throw you a few references also. Btw, I know most people don't have institutional access to scientific journals, but you can copy the URL or DOI of any paper and paste it into SciHub (a delightful Russian scientific piracy website) to get a copy of the manuscript for free. I strongly believe it's better to critically review research yourself - really see the data and see how it was analyzed - before accepting anyone's interpretation of the data. Even the researchers who generated the data may have failed to understand its implications, or may have analyzed it incorrectly with some false assumptions. That said, reading scientific papers is kind of like learning to read a new language. There is a ton of jargon which may be hard to follow. My rule of thumb when reading a paper is:

1. Read the title and abstract to see if they're talking about what you want to learn about
2. Review the figures and tables, review the captions of the figures and tables. Spend almost all of your time here. If needed, review the text near the figure to determine what it's about.
3. Review the conclusion. Does it seem like bullshit based on what you just saw in the figures and tables?
4. If the above was compelling enough, read the paper again, from the beginning. If not, find a new one.

Okay now to answer: the entourage effect appears to be the synergistic effect of two or more cannabinoids and/or terpenes with therapeutic activity that is greater than the sum of either of the components in isolation. Because of the legal status of cannabis in the U.S., there is a dearth of research on the individual effects of cannabinoids and cannabis-derived terpenes, but what little research there is shows that many of these compounds have pharmaceutical activity. The entourage effect is invoked when it can be shown that Cannabinoid 1 is less effective than Cannabinoid 1 + Cannabinoid 2 at, for example, tumor suppression.

As a pretty hardcore experimentalist myself, I'm of the opinion that the maximum therapeutic potential will be reached with custom formulations which provide just the right balance of cannabinoids and terpenes with specific activity for a specific therapy. Since that's rather hard to do, full spectrum extracts will have to suffice for now.

References:
"Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer" https://doi.org/10.1016/j.bcp.2018.06.025

"Cannabis Phytomolecule 'Entourage': From Domestication to Medical Use" https://doi.org/10.1016/j.tplants.2020.04.007

 

[Milson]

I'll take a crack at it and throw you a few references also. Btw, I know most people don't have institutional access to scientific journals, but you can copy the URL or DOI of any paper and paste it into SciHub (a delightful Russian scientific piracy website) to get a copy of the manuscript for free. I strongly believe it's better to critically review research yourself - really see the data and see how it was analyzed - before accepting anyone's interpretation of the data. Even the researchers who generated the data may have failed to understand its implications, or may have analyzed it incorrectly with some false assumptions. That said, reading scientific papers is kind of like learning to read a new language. There is a ton of jargon which may be hard to follow. My rule of thumb when reading a paper is:

1. Read the title and abstract to see if they're talking about what you want to learn about
2. Review the figures and tables, review the captions of the figures and tables. Spend almost all of your time here. If needed, review the text near the figure to determine what it's about.
3. Review the conclusion. Does it seem like bullshit based on what you just saw in the figures and tables?
4. If the above was compelling enough, read the paper again, from the beginning. If not, find a new one.

Okay now to answer: the entourage effect appears to be the synergistic effect of two or more cannabinoids and/or terpenes with therapeutic activity that is greater than the sum of either of the components in isolation. Because of the legal status of cannabis in the U.S., there is a dearth of research on the individual effects of cannabinoids and cannabis-derived terpenes, but what little research there is shows that many of these compounds have pharmaceutical activity. The entourage effect is invoked when it can be shown that Cannabinoid 1 is less effective than Cannabinoid 1 + Cannabinoid 2 at, for example, tumor suppression.

As a pretty hardcore experimentalist myself, I'm of the opinion that the maximum therapeutic potential will be reached with custom formulations which provide just the right balance of cannabinoids and terpenes with specific activity for a specific therapy. Since that's rather hard to do, full spectrum extracts will have to suffice for now.

References:
"Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer" https://doi.org/10.1016/j.bcp.2018.06.025

"Cannabis Phytomolecule 'Entourage': From Domestication to Medical Use" https://doi.org/10.1016/j.tplants.2020.04.007

Thanks for the links and tips re figures!

I guess I should have tipped my hand a bit more.

My understanding is the original conception was that, more or less, the terpenoids etc are broken down by the same enzymes that break down thc, more or less. So they essentially let the THC have an effect for longer by "occupying" the enzymes for the THC (not that there is precedence, just more overall).

However, now the same scientists who proposed that initially are claiming that the terpenoids themselves have their own business with receptors etc to attend to and they are much more than just along for the ride, more or less.

I was wondering if you had an understanding of that dynamic that would be a bit more eloquent than what I wrote lol.

 

[b3lyp631g]

Thanks for the links and tips re figures!

I guess I should have tipped my hand a bit more.

My understanding is the original conception was that, more or less, the terpenoids etc are broken down by the same enzymes that break down thc, more or less. So they essentially let the THC have an effect for longer by "occupying" the enzymes for the THC (not that there is precedence, just more overall).

However, now the same scientists who proposed that initially are claiming that the terpenoids themselves have their own business with receptors etc to attend to and they are much more than just along for the ride, more or less.

I was wondering if you had an understanding of that dynamic that would be a bit more eloquent than what I wrote lol.

It looks like a lot more is going on than simply one specific enzymatic interaction with terpenes and cannabinoids. Individual terpenes and individual cannabinoids have diverse therapeutic activity with varied mechanisms of activity. There are dozens of individual compounds, many of which have either known or unknown activity. To assume the synergy is all due to one kind of enzyme reactivity is a vast oversimplification.

 

[MIMedGrower]

I'll take a crack at it and throw you a few references also. Btw, I know most people don't have institutional access to scientific journals, but you can copy the URL or DOI of any paper and paste it into SciHub (a delightful Russian scientific piracy website) to get a copy of the manuscript for free. I strongly believe it's better to critically review research yourself - really see the data and see how it was analyzed - before accepting anyone's interpretation of the data. Even the researchers who generated the data may have failed to understand its implications, or may have analyzed it incorrectly with some false assumptions. That said, reading scientific papers is kind of like learning to read a new language. There is a ton of jargon which may be hard to follow. My rule of thumb when reading a paper is:

1. Read the title and abstract to see if they're talking about what you want to learn about
2. Review the figures and tables, review the captions of the figures and tables. Spend almost all of your time here. If needed, review the text near the figure to determine what it's about.
3. Review the conclusion. Does it seem like bullshit based on what you just saw in the figures and tables?
4. If the above was compelling enough, read the paper again, from the beginning. If not, find a new one.

Okay now to answer: the entourage effect appears to be the synergistic effect of two or more cannabinoids and/or terpenes with therapeutic activity that is greater than the sum of either of the components in isolation. Because of the legal status of cannabis in the U.S., there is a dearth of research on the individual effects of cannabinoids and cannabis-derived terpenes, but what little research there is shows that many of these compounds have pharmaceutical activity. The entourage effect is invoked when it can be shown that Cannabinoid 1 is less effective than Cannabinoid 1 + Cannabinoid 2 at, for example, tumor suppression.

As a pretty hardcore experimentalist myself, I'm of the opinion that the maximum therapeutic potential will be reached with custom formulations which provide just the right balance of cannabinoids and terpenes with specific activity for a specific therapy. Since that's rather hard to do, full spectrum extracts will have to suffice for now.

References:
"Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer" https://doi.org/10.1016/j.bcp.2018.06.025

"Cannabis Phytomolecule 'Entourage': From Domestication to Medical Use" https://doi.org/10.1016/j.tplants.2020.04.007

Thank you. I have a lot of reading to do. ;-)

And of course our experiments are less than scientific.

however

I want to add that the most pain relief and what caused Mrs. MMG internal cysts to start healing themselves was the mixing of at least 4 different plants extracts into edibles.

we have found and our patients have verified that even the effects are deeper and more complex The more and different plants we include.

like smoking a “salad” gets you higher than just a joint of one strain.

 

[beluga]

Thank you. I have a lot of reading to do. ;-)

And of course our experiments are less than scientific.

however

I want to add that the most pain relief and what caused Mrs. MMG internal cysts to start healing themselves was the mixing of at least 4 different plants extracts into edibles.

we have found and our patients have verified that even the effects are deeper and more complex The more and different plants we include.

like smoking a “salad” gets you higher than just a joint of one strain.

I can only imagine what kinds of signals your body gives with that kind of thorough prodding...

Your brain:
Your brain on drugs:
Your brain on lots of drugs:

And then I imagine a designer drug form...

Your brain on our drugs! :

 

[MIMedGrower]

I can only imagine what kinds of signals your body gives with that kind of thorough prodding...

Your brain:
Your brain on drugs:
Your brain on lots of drugs:

And then I imagine a designer drug form...

Your brain on our drugs! :

i see after “lots of drugs” you show only desert strains. Cookies, cake, etc.


i suggest you mix chem and citrus in with the cookies. ;-)

 

[beluga]

i see after “lots of drugs” you show only desert strains. Cookies, cake, etc.


i suggest you mix chem and citrus in with the cookies. ;-)

Ohhh.. haha! Whoops.
I was going for the egg-product angle and there wasn't an omelet emoji

 

[Milson]

It looks like a lot more is going on than simply one specific enzymatic interaction with terpenes and cannabinoids. Individual terpenes and individual cannabinoids have diverse therapeutic activity with varied mechanisms of activity. There are dozens of individual compounds, many of which have either known or unknown activity. To assume the synergy is all due to one kind of enzyme reactivity is a vast oversimplification.

I see....

Thank you for the answer. In the future if I have a question and you are still around, I will try to be more specific.

 

[pmoss311]

I'm a PhD chemist working mostly in the clean tech industry, but I've got a little side hustle going on where I help researchers and clients working in the hemp and cannabis industries with purification, isolation, synthesis, and custom formulation. (I also help interpret sketchy COAs). I've been involved with a pretty wide array of projects and have noticed a lot of misinformation in the hemp and cannabis communities, so I'm here to answer questions. Reach out if you have any burning questions. I am very much not an expert in plant biology or cannabis cultivation, so I'm also here to learn what it's like to grow and distribute cannabis products.

Hello, I have a question for you. You seem to know your stuff pretty well. I'm interested in converting some CBD isolate into D8. I was curious which acid, or combo of acids, that you have had the best luck with. Focusing on a couple of aspects: Yield, reaction speed, potential byproducts.

 

[Moe.Red]

As a pretty hardcore experimentalist myself, I'm of the opinion that the maximum therapeutic potential will be reached with custom formulations which provide just the right balance of cannabinoids and terpenes with specific activity for a specific therapy. Since that's rather hard to do, full spectrum extracts will have to suffice for now.

You took the words right out of my mouth.